NM_001012967.3:c.5106A>C

Variant names:

• chr4-168358162-T-G
• NM_001012967.3:c.5106A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012967.3(DDX60L):​c.5106A>C​(p.Gln1702His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX60L NM_001012967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.682
• Publications: 0 publications found

Genes affected

DDX60L (HGNC:26429): (DExD/H-box 60 like) This gene encodes a member of the DExD/H-box helicase family of proteins, a subset of the super family 2 helicases. Members of the DExD/H-box helicase family share a conserved functional core comprised of two RecA-like globular domains. These domains contain conserved motifs that mediate ATP binding, ATP hydrolysis, nucleic acid binding, and RNA unwinding. In addition to functions in RNA metabolism, members of this family are involved in anti-viral immunity and act as cytosolic sensors of viral nucleic acids. The protein encoded by this gene has been shown to inhibit hepatitis C virus replication in response to interferon stimulation in cell culture. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0669643).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX60L	NM_001012967.3	MANE Select	c.5106A>C	p.Gln1702His	missense	Exon 38 of 38	NP_001012985.2	Q5H9U9-1
	DDX60L	NM_001345927.2		c.5109A>C	p.Gln1703His	missense	Exon 38 of 38	NP_001332856.1
	DDX60L	NM_001378072.1		c.5109A>C	p.Gln1703His	missense	Exon 39 of 39	NP_001365001.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX60L	ENST00000682922.1	MANE Select	c.5106A>C	p.Gln1702His	missense	Exon 38 of 38	ENSP00000507872.1	Q5H9U9-1
	DDX60L	ENST00000854594.1		c.5109A>C	p.Gln1703His	missense	Exon 38 of 38	ENSP00000524653.1
	DDX60L	ENST00000511577.5	TSL:5	c.5106A>C	p.Gln1702His	missense	Exon 38 of 38	ENSP00000422423.1	Q5H9U9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.94
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.039	N
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.68
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.042
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.11
MutPred		0.11		Loss of solvent accessibility (P = 0.0238)
MVP		0.014
MPC		0.028
ClinPred		0.13	T
GERP RS		0.52
gMVP		0.34
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-169279313;